16-55528447-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017839.5(LPCAT2):c.382G>A(p.Val128Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0067 in 1,613,998 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0068 (70 hom.)
• Consequence: LPCAT2 NM_017839.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.62

Genes affected

LPCAT2 (HGNC:26032): (lysophosphatidylcholine acyltransferase 2) This gene encodes a member of the lysophospholipid acyltransferase family. The encoded enzyme may function in two ways: to catalyze the biosynthesis of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) from 1-O-alkyl-sn-glycero-3-phosphocholine, and to catalyze the synthesis of glycerophospholipid precursors from arachidonyl-CoA and lysophosphatidylcholine. The encoded protein may function in membrane biogenesis and production of platelet-activating factor in inflammatory cells. The enzyme may localize to the endoplasmic reticulum and the Golgi. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009516329).
• BP6: Variant 16-55528447-G-A is Benign according to our data. Variant chr16-55528447-G-A is described in ClinVar as [Benign]. Clinvar id is 773582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00684 (9993/1461722) while in subpopulation MID AF= 0.0373 (215/5762). AF 95% confidence interval is 0.0332. There are 70 homozygotes in gnomad4_exome. There are 5189 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPCAT2	NM_017839.5	c.382G>A	p.Val128Ile	missense_variant	3/14	ENST00000262134.10
LPCAT2	XM_047434277.1	c.214G>A	p.Val72Ile	missense_variant	3/14
LPCAT2	XM_005256006.4	c.382G>A	p.Val128Ile	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPCAT2	ENST00000262134.10	c.382G>A	p.Val128Ile	missense_variant	3/14	1	NM_017839.5	P1
LPCAT2	ENST00000564084.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00543 AC: 826 AN: 152158 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00693

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00725 AC: 1820 AN: 251202 Hom.: 20 AF XY: 0.00812 AC XY: 1103 AN XY: 135754

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00507

Gnomad ASJ exome AF: 0.0286

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0122

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00766

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.00684 AC: 9993 AN: 1461722 Hom.: 70 Cov.: 33 AF XY: 0.00714 AC XY: 5189 AN XY: 727158

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.00602

Gnomad4 ASJ exome AF: 0.0275

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0122

Gnomad4 FIN exome AF: 0.000955

Gnomad4 NFE exome AF: 0.00639

Gnomad4 OTH exome AF: 0.00871

GnomAD4 genome AF: 0.00543 AC: 827 AN: 152276 Hom.: 2 Cov.: 33 AF XY: 0.00530 AC XY: 395 AN XY: 74462

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00694

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00771 Hom.: 14

Bravo AF: 0.00583

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0107 AC: 92

ExAC AF: 0.00764 AC: 928

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0095	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.74	N
REVEL	Uncertain	0.47
Sift	Benign	0.14	T
Sift4G	Benign	0.21	T
Polyphen		0.84	P
Vest4		0.21
MVP		0.88
MPC		0.64
ClinPred		0.058	T
GERP RS		5.8
Varity_R		0.21
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61739979; hg19: chr16-55562359;